MRI-Based Interstitial Fluid Velocity Analysis for Drug Delivery Efficiency Evaluation in Tumor

Abstract

There are many flow behaviors in solid tumors, including intravascular, bloodstream, and interstitial convection. Studies have shown that tumor interstitial fluid (TIF) is an important part of tumor microenvironment regulation and affects drug delivery and metabolism between tumor cells. Magnetic resonance imaging (MRI) is suitable for detecting the flow rates of liquids in tissues. Clinical phase contrast PC-MRI technology has been designed to observe the blood flow in large vessels such as arteries and veins; however, it is not sensitive enough to deal with slow flow velocity. Our previously developed vertical plane echo PC-MRI technology, the Velocity Mapping sequence, improved the signal-to-noise ratio (SNR) for measuring slow interstitial fluid rate. In this study, this sequence was used to determine the TIF flow rate in MDA-MB-231 human breast tumor cells used in BALB/c nude male mice. Two different sizes of contrast agents were intravenously injected, and the relationship between their distribution and the TIF flow rate was studied for the first time. Combining the results of clinical scanning showed that small-molecule DTPA-Gd (diethylenetriaminepentaacetic acid-gadolinium) was distributed immediately around the tumor margin after the injection. This distribution was positively correlated to the high flow rate area of the TIF before administration. In contrast, nanoparticles NaGdF 4 −PEG (polyethylene glycol) entered the tumor and reached their peak at 3 h. Drug distribution was negatively correlated with the high-flow-rate region of the TIF. Investigation of the TIF velocity can help better understand the fluid behavior in tumors and its role in drug delivery.

Exploring multiple bioprocess monitoring modalities for Large-scale 3D Bioprinted Tissue Cultivation

“…Quali cation and characterisation tools must align with in vivo measurement techniques. Magnetic Resonance Imaging (MRI) stands out as a reference tool for both in vivo and in vitro tissue imaging 13,16,17 . Indeed, MRI offers high spatial resolution from 2 mm 3 in the clinical routine down to 300 µm3 in dedicated MRI systems and a high imaging depth of 0.1 mm up to 40 cm 9,13 .…”

“…MRI has been employed for uid velocity mapping in an in vivo tumour environment. To reach a resolution of 133 mm 3 its capabilities was enhanced using contrast agents 17 . Overall, there is a tradeoff between spatial resolution and penetration depth of the imaging modality.…”